Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

12 Issues per year


IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

Online
ISSN
1437-4331
See all formats and pricing
More options …
Volume 56, Issue 1

Issues

The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature

Federica de Liso
  • Corresponding author
  • Laboratorio di analisi chimico cliniche e microbiologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Milan, Italy, Phone: +255032582, Fax: +255032397
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Caterina Matinato
  • Laboratorio di analisi chimico cliniche e microbiologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mariangela Ronchi
  • Laboratorio di analisi chimico cliniche e microbiologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rita Maiavacca
  • Laboratorio di analisi chimico cliniche e microbiologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-07-21 | DOI: https://doi.org/10.1515/cclm-2017-0249

Abstract

Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%–95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods. More recently, new biomarkers have been evaluated in order to improve the diagnostic sensitivity, such as kelch-like 12 (KLHL12) and hexokinase-1. Considering these different serum biomarkers, studies evaluating their diagnostic role in AMA-negative PBC patients compared to AMA-positive ones and controls were included in this review. Pooled sensitivity and specificity were 37% and 85%, respectively. The overall PPV and NPV mean values were 45% and 83%. Even if all biomarkers are very specific for PBC, the overall sensitivity was poor and therefore is necessary to identify a marker with a greater sensitivity for PBC in AMA-negative patients.

Keywords: anti-mitochondrial antibodies negative patients; primary biliary cholangitis; primary biliary cirrhosis; serum biomarkers

References

  • 1.

    Leuschner U. Primary biliary cirrhosis – presentation and diagnosis. Clin Liver Dis 2003;7:741–58.PubMedCrossrefGoogle Scholar

  • 2.

    Granito A, Yang WH, Muratori L, Lim MJ, Nakajima A, Ferri S, et al. PML nuclear body component sp140 is a novel autoantigen in primary biliary cirrhosis. Am J Gastroenterol 2010;105:125–31.CrossrefWeb of SciencePubMedGoogle Scholar

  • 3.

    Liu B, Shi XH, Zhang FC, Zhang W, Gao LX. Antimitochondrial antibody-negative primary biliary cirrhosis: a subset of primary biliary cirrhosis. Liver Int 2008;28:233–9.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 4.

    Gao L, Tian X, Liu B, Zhang F. The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med 2008;8:9–15.CrossrefWeb of SciencePubMedGoogle Scholar

  • 5.

    Granito A, Muratori P, Muratori L, Pappas G, Cassani F, Worthington J, et al. Antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim-like/membranous’ patterns: diagnostic accuracy for primary biliary cirrhosis. Aliment Pharmacol Ther 2006;24:1575–83.CrossrefPubMedGoogle Scholar

  • 6.

    Ueno Y, Ishii M, Takahashi S, Mano Y, Yahagi K, Kisara N, et al. Primary biliary cirrhosis with antibody against carbonic anhydrase II associates with distinct immunological backgrounds. Hepatol Res 2001;20:18–27.CrossrefPubMedGoogle Scholar

  • 7.

    Muratori P, Muratori L, Lenzi M, Bianchi FB. Antibodies to carbonic anhydrase in autoimmune cholangiopathy. Gastroenterolgy 1997;112:1053–4.CrossrefGoogle Scholar

  • 8.

    Gordon SC, Quattrociocchi-Longe TM, Khan BA, Kodali VP, Chen J, Silverman AL, et al. Antibodies to carbonic anhydrase in patients with immune cholangiopathies. Gastroenterology 1995;108:1802–9.CrossrefPubMedGoogle Scholar

  • 9.

    Norman GL, Yang CY, Ostendorff HP, Shums Z, Lim MJ, Wang J, et al. Anti-kelch-like 12 and anti-hexokinase 1: novel autoantibodies in primary biliary cirrhosis. Liver Int 2015;35:642–51.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 10.

    Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097.CrossrefPubMedGoogle Scholar

  • 11.

    Heathcote EJ. Management of primary biliary cirrhosis. The American Association for the study of liver disease practice guidelines. Hepatology 2000;31:1005–13.Google Scholar

  • 12.

    Rigopoulou EI, Davies ET, Pares A, Zachou K, Liaskos C, Bogdanos DP, et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis. Gut 2005;54:528–32.PubMedCrossrefGoogle Scholar

  • 13.

    Muratori P, Muratori L, Ferrari R, Cassani F, Bianchi G, Lenzi M, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol 2003;98:431–7.PubMedCrossrefGoogle Scholar

  • 14.

    Invernizzi P, Crosignani A, Battezzati PM, Covini G, De Valle G, Larghi A, et al. Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology 1997;25:1090–5.CrossrefPubMedGoogle Scholar

  • 15.

    Comay D, Cauch-Dudek K, Hemphill D, Diamandis E, Wanless I, Heathcote EJ. Are antibodies to carbonic anhydrase II specific for anti-mitochondrial antibody-negative primary biliary cirrhosis? Dig Dis Sci 2000;45:2018–21.PubMedCrossrefGoogle Scholar

  • 16.

    Invernizzi P, Battezzati PM, Crosignani A, Zermiani P, Bignotto M, Del Papa N, et al. Antibody to carbonic anhydrase II is present in primary biliary cirrhosis (PBC) irrespective of antimitochondrial antibody status. Clin Exp Immunol 1998;114:448–54.PubMedCrossrefGoogle Scholar

  • 17.

    Bizzaro N, Covini G, Rosina F, Muratori P, Tonutti E, Villalta D, et al. Overcoming a “portable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol 2012;42:288–97.CrossrefGoogle Scholar

About the article

Received: 2017-03-22

Accepted: 2017-06-09

Published Online: 2017-07-21

Published in Print: 2017-11-27


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages 25–31, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0249.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in